Publication Date

2019

Document Type

Thesis

Committee Members

Yong-jie Xu, M.D., Ph.D. (Advisor); Michael G. Kemp, Ph.D. (Committee Member); Dawn P. Wooley, Ph.D. (Committee Member); Nancy J. Bigley, Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

In response to various perturbations of DNA replication, the DNA replication checkpoint is activated in eukaryotes to stimulate a cascade of cellular responses that are crucial for maintaining genome stability and cell survival. Defects in the checkpoint pathway result in mutations and genome instability, which is a hallmark for cancers. This study used a genetic approach to identify a mutation in the MMS (methyl methanesulfonate) and UV-sensitive protein Mus81, a DNA repair enzyme that resolves aberrant DNA structures through the homologous recombination pathway. We show that a single missense mutation, identified in fission yeast mus81-1, causes moderate reduction in the phosphorylation levels of the major DNA replication checkpoint proteins Mrc1(Claspin) and Cds1(Chk2) in fission yeast. We also show that the mutation directly affects the DNA repair and the DNA damage checkpoint mediated by Chk1 that causes dramatic cell lethality in mus81-1 mutant upon treatment with the DNA damaging agents: MMS, UV and Bleomycin.

Page Count

50

Year Degree Awarded

2019


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